From the Guidelines
Chromophobe renal cell carcinoma (RCC) should be treated with surgical resection as the primary treatment, and for metastatic disease, sunitinib or everolimus may be considered as first-line systemic treatment options, as suggested by the ESMO clinical practice guidelines 1.
Treatment Options
- Surgical resection, either partial nephrectomy for smaller, localized tumors or radical nephrectomy for larger tumors, is the primary treatment for chromophobe RCC.
- For metastatic disease, targeted therapies such as tyrosine kinase inhibitors (sunitinib, pazopanib) or mTOR inhibitors (everolimus) may be used, though evidence for their efficacy specifically in chromophobe RCC is limited compared to clear cell RCC 1.
- Some patients with chromophobe RCC may benefit from mTOR inhibitors since mutation on chromosome 7 was shown to lead to a loss of the folliculin gene with upregulation of mTOR 1.
Prognosis and Characteristics
- Chromophobe RCC accounts for 5–7% of all RCC and has a better prognosis compared to clear cell RCC, with a 5-year survival rate of about 80-90% 1.
- Chromophobe RCC typically presents as a well-circumscribed, solid tumor with a light brown or tan color on cut section, and is characterized by large, pale cells with prominent cell membranes and perinuclear halos.
- Evaluation of a large ChRCC cohort showed that pT stage, tumor necrosis, and sarcomatoid change were independently predictive of aggressive behavior in multivariable analysis 1.
Follow-up and Monitoring
- Regular follow-up imaging is essential after treatment to monitor for recurrence.
- The improved prognosis of chromophobe RCC is attributed to its typically lower grade, less aggressive behavior, and lower tendency to metastasize compared to other RCC subtypes.
From the Research
Characteristics of Chromophobe RCC
- Chromophobe renal cell carcinoma (ChRCC) is the second most common variant histology (non-clear cell) RCC 2
- ChRCC is distinct from clear cell RCC (ccRCC) in terms of genetics, genomics, metabolism, cell of origin, and response to targeted and immune therapies 2
- ChRCC typically has a favorable clinical course and is considered to have a better prognosis, with earlier stage tumors and longer overall survival compared with clear cell RCC 3
Pathogenesis and Treatment
- The pathogenesis of ChRCC remains unclear, but current data suggest two potential mechanisms: mTORC1 hyperactivation through PTEN pathway mutations and mitochondrial dysfunction leading to oxidative stress 2
- There are no specific approved treatments for ChRCC, although some responses to tyrosine kinase and mTOR inhibitors have been observed 2
- Sunitinib is a standard treatment for metastatic clear cell renal cell carcinoma (mccRCC) and may be associated with similar outcome and toxicities as in metastatic chromophobe renal cell carcinoma (mchRCC) 4
Imaging and Histologic Findings
- At gross pathologic analysis, ChRCC is a solid well-defined mass with lobulated borders 5
- Histologic findings include large pale polygonal cells with abundant transparent cytoplasm, crinkled "raisinoid" nuclei with perinuclear halos, and prominent cell membranes 5
- The most common imaging pattern is a predominantly solid renal mass with circumscribed margins and enhancement less than that of the renal cortex 5
Prognosis and Outcome
- ChRCC accounts for almost 5% of total RCC cases and carries the best prognosis among the rest of RCC types 6
- However, patients with metastatic ChRCC disease have worse prognosis than patients with advanced clear cell RCC 6
- The optimum therapy for metastatic ChRCC is still missing, as results from ongoing trials are awaited 6